Human giant larvae-1 promotes migration and invasion of malignant glioma cells by regulating N-cadherin.
Human giant larvae-1 promotes migration and invasion of malignant glioma cells by regulating N-cadherin.
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Human Giant larvae-1通过调节N-cadherin促进恶性胶质瘤细胞迁移和侵袭
DOI：
10.3892/ol.2021.12428
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发表时间：
2021-03
期刊：
影响因子：
2.9
通讯作者：
Zhou X
中科院分区：
文献类型：
--
作者：
Wang Y;Zhang Y;Sang B;Zhu X;Yu R;Zhou X
人巨幼虫-1（Hugl-1）是果蝇肿瘤抑制因子致死巨幼虫的人类同源物，并已被报道参与人类恶性肿瘤的发展。我们小组先前的研究表明，Hugl-1在裸鼠颅内模型中抑制胶质瘤细胞增殖。然而，Hugl-1参与胶质瘤侵袭和迁移以及去极化过程的确切分子机制在很大程度上仍然未知。本研究利用稳定表达Hugl-1的U251-MG细胞，通过创伤愈合、Transwell侵袭和western blot检测，探讨Hugl-1在胶质瘤侵袭和迁移中的作用及其具体机制。本研究的结果表明，Hugl-1的过表达降低了细胞-细胞粘附，并增加了细胞-细胞外基质粘附。此外，Hugl-1的过表达促进伪足形成、胶质瘤细胞迁移和侵袭。分子作用机制涉及Hugl-1对N-钙粘蛋白水平的负调节。过表达或敲低N-cadherin分别部分抑制或增强Hugl-1对胶质瘤细胞迁移和侵袭的作用。此外，Hugl-1抑制细胞增殖，同时促进细胞迁移，这表明它可能在细胞过程中发挥双面生物学作用。综上所述，这些结果表明Hugl-1通过降低N-cadherin表达促进恶性胶质瘤细胞的迁移和侵袭。因此，Hugl-1可用于开发靶向和个性化治疗。
Human giant larvae-1 (Hugl-1) is a human homologue of Drosophila tumor suppressor lethal -giant larvae and has been reported to be involved in the development of human malignancies. Previous studies performed by our group demonstrated that Hugl-1 inhibits glioma cell proliferation in an intracranial model of nude mice. However, the exact molecular mechanisms underlying the participation of Hugl-1 in glioma invasion and migration, and in the depolarizing process remain largely unknown. Utilizing the U251-MG cells with stable expression of Hugl-1, the present study used wound healing, Transwell invasion and western blot assays to explore the role and specific mechanism of Hugl-1 in glioma invasion and migration. The results of the present study demonstrated that overexpression of Hugl-1 decreased cell-cell adhesion and increased cell-cell extracellular matrix adhesion. In addition, overexpression of Hugl-1 promoted pseudopodia formation, glioma cell migration and invasion. The molecular mechanism of action involved the negative regulation of N-cadherin protein levels by Hugl-1. Overexpression or knockdown of N-cadherin partially suppressed or enhanced the effects of Hugl-1 on glioma cell migration and invasion, respectively. Furthermore, Hugl-1 inhibited cell proliferation, while promoting cell migration, which suggests that it may serve a two-sided biological role in cellular processes. Taken together, these results suggest that Hugl-1 promotes the migration and invasion of malignant glioma cells by decreasing N-cadherin expression. Thus, Hugl-1 may be applied in the development of targeted and personalized treatment.
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影响因子：
8
作者：
Grifoni, D;Garoia, F;Strand, D
通讯作者：
Strand, D
DOI：
10.1615/critreveukaryotgeneexpr.2018020775
发表时间：
2018-01-01
影响因子：
1.6
作者：
Bhattacharya, Susinjan
通讯作者：
Bhattacharya, Susinjan
细胞形状和细胞间粘附调节有丝分裂纺锤体方向
影响因子：
3.3
作者：
Li, Jingchen;Cheng, Longcan;Jiang, Hongyuan
通讯作者：
Jiang, Hongyuan
影响因子：
2.7
作者：
Huang，Chaolie;Kratzer，Marie-Claire;Kashef，Jubin
通讯作者：
Kashef，Jubin
影响因子：
3.3
作者：
Han, Zheng-Xiang;Wang, Xiao-Xia;Zheng, Jun-Nian
通讯作者：
Zheng, Jun-Nian